Cell death is a feature of many diseases as well as therapeutic methods, for example in the treatment of cancer. It is therefore desirable to be able to measure cell death, to assess either the status of a disease that involves cell death or the effect of a treatment that induces cell death. In recent years two distinct mechanisms of cell death known as apoptosis and necrosis have been described. While distinct in certain aspects, these two forms of cell death can also be viewed as extremes along a continuum, such that late-stage apoptosis overlaps with necrosis.
Apoptosis, which is also known as programmed cell death, is generally characterized as an energy-dependent, genetically controlled process by which cell death is activated through an internally regulated suicide program. Features of apoptosis generally include phosphatidylserine externalization, loss of membrane integrity, cytoplasm shrinkage, chromatin and nucleus condensation, DNA degradation, and fragmentation of the cell into smaller apoptotic bodies by a budding process. Normally the resulting apoptotic bodies are phagocytosed by macrophages and neighboring cells without inducing an inflammatory response. Methods frequently used to assess apoptosis include staining by fluorescently labeled annexin A5 (also known as Annexin V) and terminal uridine deoxynucleotidyl end-labeling (TUNEL) assay.
Necrosis, which is also known as accidental cell death, is typically induced by any of a variety of sudden, severe, non-physiological insults, for example physical, chemical, and ischemic insults. The process is generally characterized by progressive cell swelling, denaturation and coagulation of cytoplasmic proteins, disintegration of subcellular organelles and irreversible collapse of the plasma membrane integrity. This latter feature permits leakage of cytotoxic and other cellular components, inducing a local inflammatory response.
Loss of membrane integrity, a feature common to both apoptosis and necrosis, allows intracellular components to leak out of cells. As such, serum and plasma levels of intracellular components such as the lactate dehydrogenase (LDH) protein have been used as surrogate markers of cell death, i.e., necrosis and late-stage apoptosis.